Cancer of the prostate is a disease of unknown etiology. The long-term goals are to identify factors which lead to the development of prostatic carcinoma in man. Proposed studies are based on the idea that those factors which promote cell proliferation and affect differentiation of normal cells may become determining factors in the development of neoplasia. The specific objectives are: 1) to identify factors which affect growth and differentiation of normal prostatic epithelium in vivo and in cell culture. The central role of testosterone in normal prostate development is acknowledged. However, we propose the hypothesis that other hormones like insulin, prolactin and thyroxine are also involved directly and indirectly by interacting with testosterone. We will therefore examine in vitro, the effects of these hormones on the growth and differentiation of normal human prostatic epithelium, their synergistic and antagonistic effects with each other and their interaction with 5-alpha-dihydrotestosterone; 2) to determine the role of these hormones as cofactors in carcinogenesis in prostatic epithelium of the aging male; 3) to identify other hormones, growth factors, polyamines and trace metals like zinc which may affect growth and maintenance of prostatic epithelium in vivo and in vitro; use these agents to develop a chemically defined medium and to develop an in vitro cell model system; 4) to examine differentiated function by measuring secretory products of prostatic epithelium, e.g., plasminogen activator, citrate and acid phosphatase and by examining cell ultrastructure; 5) to develop methods for subculture. Effects of hormones and other factors a) on growth will be determined by dose response studies, growth curves, densitometry and measurement of DNA, RNA and protein synthesis and b) on differentiation by light and electron microscopic examination and by measurement of plasminogen activator, citrate and acid phosphatase using in vitro and cytochemical techniques. Proposed studies will make significant contributions to our knowledge of the etiology, prevention, detection and treatment of prostatic cancer in man.